Patient
BMA-BCL2_EXPRESSION_AML · Algorithm: ALGO-AML-1L
Clinical significance of mutations (ESCAT)
Tumor-board context — the engine does not use these tiers to rank tracks
| Biomarker | Variant | ESCAT | Evidence | Clinical significance | Drugs | Sources |
|---|
| BIO-BCL2-IHC | BCL2 protein overexpression by IHC (H-score ≥100 or ≥50% cells 1+/2+/3+) OR BCL2-expressing AML (flow cytometry positivity); note: FDA approval for venetoclax in AML is NOT restricted to BCL2+ patients — overexpression is a predictive enrichment biomarker, not a companion diagnostic | IIB | - SRC-VIALE-A-DINARDO-2020: Level A (Supports, Sensitivity/Response)
- SRC-NCCN-AML-2025: Level Category 1 (Supports, Sensitivity/Response)
- SRC-ELN-AML-2022: Level A (Supports, Sensitivity/Response)
| Venetoclax (BCL2 inhibitor) + azacitidine or decitabine is FDA-approved (Oct 2020) for newly diagnosed AML in patients ≥75 years or those ineligible for intensive induction chemotherapy, regardless of BCL2 expression status. However, BCL2 protein overexpression and specific co-mutations (IDH1/2, NPM1) are strong predictors of venetoclax response. VIALE-A trial (DiNardo et al. NEJM 2020 — venetoclax + azacitidine vs azacitidine): mOS 14.7 vs 9.6 mo (HR 0.66, p<0.001); CR/CRi rate 66.4% vs 28.3%. BCL2 IHC high-expressors had superior outcomes in retrospective VIALE-A subanalyses. Molecular co-mutation context: NPM1-mutated AML: CR ~75% with ven+aza; IDH2-mutated: CR ~67%; IDH1-mutated: CR ~57%; TP53-mutated: CR ~40% (inferior). AML with t(8;21) or inv(16) (CBF-AML): poor ven response — avoid ven+aza in favor of intensive 7+3 + GO when fit. ESCAT IIB reflects that BCL2 IHC alone is not a mandated companion diagnostic — clinical eligibility criteria (age/fitness) are the primary drivers; BCL2 overexpression adds predictive value in molecular context. | venetoclax 400 mg/day PO + azacitidine 75 mg/m² SC/IV days 1-7 (28-day cycles; VIALE-A regimen — preferred)
venetoclax 400 mg/day PO + decitabine 20 mg/m² IV days 1-5 (28-day cycles; VIALE-C alternative) | - SRC-NCCN-AML-2025
- SRC-ELN-AML-2022
- SRC-VIALE-A-DINARDO-2020
|
Treatment options (4 tracks)
- Indication
- IND-AML-1L-7-3
- Regimen
- 7+3 Induction (cytarabine + daunorubicin/idarubicin) ± midostaurin
- Drugs + NSZU
- Cytarabine (DRUG-CYTARABINE) 100-200 mg/m²/day · continuous IV infusion days 1-7 · IV ✓ NSZU covered
- Daunorubicin (DRUG-DAUNORUBICIN) 60-90 mg/m² (or idarubicin 12 mg/m² as alternative) · IV bolus days 1-3 · IV ✓ NSZU covered
- Midostaurin (DRUG-MIDOSTAURIN) 50 mg PO BID — ONLY if FLT3-ITD/TKD positive · days 8-21 of induction (and continuation through consolidation + maintenance) · PO ⚠ NSZU — not for this indication
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Reason
- Engine default per algorithm ALGO-AML-1L: {'step': 7, 'outcome': False, 'branch': {'result': 'IND-AML-1L-7-3'}, 'fired_red_flags': [], 'winner_red_flag': None}
- Indication
- IND-AML-1L-VEN-AZA
- Regimen
- Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule
- Drugs + NSZU
- Venetoclax (DRUG-VENETOCLAX) Cycle 1 ramp: day 1 = 100 mg, day 2 = 200 mg, day 3 = 400 mg → days 4-28 = 400 mg PO daily; subsequent cycles = 400 mg daily continuously · PO daily; reduce to ~70-100 mg if combined with strong CYP3A4 inhibitor (posaconazole) · PO ⚠ NSZU — not for this indication
- Azacitidine (DRUG-AZACITIDINE) 75 mg/m²/day · SC or IV days 1-7 of each 28-day cycle · SC ⚠ NSZU — not for this indication
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-AML-1L-7-3-GO-CBF
- Regimen
- 7+3 + fractionated gemtuzumab ozogamicin (CD33+ AML, 1L; ALFA-0701)
- Drugs + NSZU
- Cytarabine (DRUG-CYTARABINE) 100-200 mg/m²/day · Continuous IV infusion days 1-7 · IV ✓ NSZU covered
- Daunorubicin (DRUG-DAUNORUBICIN) 60 mg/m² (per ALFA-0701; 90 mg/m² acceptable when GO not added per ECOG-ACRIN — but 60 mg/m² standard with concurrent GO due to additive cardiotoxicity / mortality concern) · IV bolus days 1-3 · IV ✓ NSZU covered
- Gemtuzumab ozogamicin (DRUG-GEMTUZUMAB-OZOGAMICIN) 3 mg/m² (max 4.5 mg total per dose) IV — fractionated · Days 1, 4, 7 of induction · IV ✗ Not registered in UA
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-LVEF-LOW-FOR-ANTHRACYCLINE
- Reason
- Alternative track presented for HCP consideration
- Indication
- IND-AML-1L-CPX351-SECONDARY
- Regimen
- CPX-351 (Vyxeos) for tAML / AML-MRC 1L
- Drugs + NSZU
- Liposomal cytarabine-daunorubicin (DRUG-CPX-351) Induction 100 units/m² IV (= cytarabine 100 mg/m² + daunorubicin 44 mg/m²) days 1, 3, 5 · Cycle 1; re-induction days 1, 3 if needed · IV ✗ Not registered in UA
- Liposomal cytarabine-daunorubicin (DRUG-CPX-351) Consolidation 65 units/m² IV days 1, 3 · Up to 2 consolidation cycles, every 5-8 weeks after count recovery · IV ✗ Not registered in UA
- Supportive care
- SUP-TLS-PROPHYLAXIS, SUP-PJP-PROPHYLAXIS, SUP-HSV-PROPHYLAXIS, SUP-HBV-PROPHYLAXIS
- Hard contraindications
- CI-LVEF-LOW-FOR-ANTHRACYCLINE
- Reason
- Alternative track presented for HCP consideration
Pre-treatment investigations
Investigations before treatment start · critical / standard / desired · merged across tracks
| ID | Name | Priority | Category | Where to order | Needed for |
|---|
| TEST-BM-ASPIRATE | Bone Marrow Aspirate | Critical | histology | — | all tracks |
| TEST-BM-TREPHINE | Bone Marrow Trephine | Critical | histology | — | all tracks |
| TEST-CBC | Complete Blood Count with Differential | Critical | lab | — | all tracks |
| TEST-CMP | Comprehensive Metabolic Panel | Critical | lab | — | all tracks |
| TEST-COAG-PANEL | Coagulation Panel | Critical | lab | — | all tracks |
| TEST-FISH-PANEL | FISH (Fluorescence In Situ Hybridization) | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-FLOW-CYTOMETRY | Flow Cytometry | Critical | histology | CSD Lab ✓ (code TBC) | all tracks |
| TEST-HBV-SEROLOGY | Hepatitis B Serology Panel (HBsAg, anti-HBc total, anti-HBs) | Critical | lab | — | all tracks |
| TEST-HCV-ANTIBODY | HCV Antibody | Critical | lab | — | all tracks |
| TEST-HIV-SEROLOGY | HIV Antibody/Antigen | Critical | lab | — | all tracks |
| TEST-KARYOTYPE | Karyotype | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-LDH | Lactate Dehydrogenase | Critical | lab | — | all tracks |
| TEST-LFT | Liver Function Tests (ALT, AST, bilirubin, ALP, GGT, albumin) | Critical | lab | — | all tracks |
| TEST-NGS-MYELOID-PANEL | Myeloid NGS Panel | Critical | genomic | CSD Lab ✓ (code TBC) | all tracks |
| TEST-PERIPHERAL-SMEAR | Peripheral Blood Smear | Critical | lab | CSD Lab ✓ (code TBC) | all tracks |
| TEST-PREGNANCY | Beta-HCG | Critical | lab | — | aggressive |
| TEST-CMV-SEROLOGY | CMV IgG/IgM | Standard | lab | — | aggressive |
| TEST-ECHO | Echocardiography | Standard | imaging | — | aggressive |
| TEST-URIC-ACID | Serum Uric Acid | Standard | lab | — | all tracks |
| TEST-D-DIMER | D-Dimer | Desired | lab | — | aggressive |
Red flags — PRO / CONTRA aggressive
PRO-AGGRESSIVE
Triggers that push toward the aggressive track
- AML with core-binding-factor (CBF) cytogenetics: t(8;21)(q22;q22.1) with RUNX1::RUNX1T1 fusion OR inv(16)(p13.1q22) / t(16;16)(p13.1;q22) with CBFB::MYH11 fusion. ~10-15% of de novo adult AML, ~25% of pediatric AML. ELN 2022 favorable risk; standard 7+3 induction + 3-4 cycles HiDAC consolidation is curative-intent in CR1 (5-year OS 60-75%); upfront alloHCT is NOT recommended in CR1 default. Adding gemtuzumab ozogamicin to induction (ALFA-0701, AML-19) further improves OS specifically in CBF AML (HR 0.69). c-KIT mutations (D816, exon-8) co-occur in ~25% of CBF AML and may downgrade favorability — warrant MRD-directed approach.
RF-AML-CORE-BINDING-FACTOR-FAVORABLE
- AML emergency triad: hyperleukocytosis (WBC ≥100 K/μL), tumor lysis syndrome (LDH >2× ULN, uric acid >7.5 mg/dL, K+ rising, phosphate rising, Ca2+ falling), or symptomatic leukostasis (dyspnea, altered mental status, retinal hemorrhage)RF-AML-EMERGENCY-TLS-LEUKOSTASIS
- AML with FLT3-ITD or FLT3-TKD mutation — addition of midostaurin (or gilteritinib in r/r) to induction is required (RATIFY trial)RF-AML-FLT3-ACTIONABLE
- AML with adverse-risk biology per ELN 2022: TP53 mutation, complex / monosomal karyotype, RUNX1 / ASXL1 mutation, KMT2A rearrangement (other than t(9;11)), inv(3) / t(3;3), -5/del(5q), -7, FLT3-ITD without NPM1, or therapy-relatedRF-AML-HIGH-RISK-BIOLOGY
- AML patient with positive HBV / HCV / HIV serology, latent TB, or active uncontrolled infection — needs antiviral prophylaxis (HBV-active prophylaxis with entecavir/tenofovir; HCV expert consult; ART optimization for HIV; TB treatment) before inductionRF-AML-INFECTION-SCREENING
- NPM1 mutation (most commonly type-A: c.860_863dupTCTG / p.W288fs) in AML — ~30% of adult AML; ~50% of cytogenetically normal AML. ELN-2022 favorable risk when NPM1-mutated WITHOUT FLT3-ITD; standard 7+3 induction first-line (no upfront alloHCT in CR1; consolidation HiDAC × 3-4 cycles is curative-intent). MRD qPCR (NPM1-mut transcript) for monitoring.
RF-AML-NPM1-MUT-FAVORABLE
- AML eligible for CPX-351 (Vyxeos) liposomal cytarabine+daunorubicin per the FDA-approved subset: therapy-related AML (t-AML, post-cytotoxic / post-radiation), AML with myelodysplasia-related changes (AML-MRC) per WHO criteria (multilineage dysplasia OR MDS-related cytogenetics OR antecedent MDS/CMML). Phase-3 Lancet 2018 (Lancet 2018;392:2088; Lancet Haematology 2020;7:e552 5-yr follow-up): mOS 9.56 vs 5.95 mo for 7+3, HR 0.69; 5-yr OS 18% vs 8%. Eligibility window age 60-75 + fit-for-intensive-chemo. Routes 1L AML to CPX-351-SECONDARY indication over standard 7+3 when this RF fires.
RF-AML-SECONDARY-AML-MRC-CPX351-ELIGIBLE
- AML refractory or relapsed: <5% blast clearance after induction, or relapse after CR (early relapse <6 mo, late relapse ≥6 mo). Switch to salvage chemotherapy (FLAG-IDA, MEC) ± targeted (FLT3+: gilteritinib; IDH+: ivosidenib/enasidenib) + alloHCT bridgeRF-AML-TRANSFORMATION-PROGRESSION
CONTRA-AGGRESSIVE
Hard contraindications to escalation
- Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE
- Pre-treatment LVEF <50% is an absolute contraindication to anthracycline-containing regimens (R-CHOP, Pola-R-CHP, ABVD, BV-AVD, etc.). Cardiotoxicity from doxorubicin is dose-cumulative and often irreversible; starting with already-impaired function risks acute decompensation.CI-LVEF-LOW-FOR-ANTHRACYCLINE
What NOT to do
Explicit prohibitive rules, each grounded in a regimen / supportive care / contraindication entity
Aggressive plan (IND-AML-1L-7-3)
- Do not start induction without baseline echo / LVEF if there is any cardiac suspicion — cumulative anthracycline cardiotoxicity can be fatal.
- Do not wait for FLT3 results to start d1-d7 cytarabine + anthracycline — midostaurin starts on day 8, so induction is not delayed.
- Do not skip TLS prophylaxis (allopurinol ± rasburicase) in patients with high WBC or high tumor activity.
- Do not skip HBV/HCV/HIV screening before induction — HBV reactivation on chemotherapy can be fatal.
- Do not prescribe without discussing fertility in young patients — anabolic-induced gonadotoxicity is often irreversible.
- Do not start without a validated donor search for ELN-adverse-risk patients — the alloHCT window closes quickly.
Standard plan (IND-AML-1L-VEN-AZA)
- Do not skip the 3-day venetoclax ramp + TLS prophylaxis — fatal TLS cases described when skipping the ramp.
- Do not use full-dose venetoclax (400 mg) with a strong CYP3A4 inhibitor (azole) — reduction to ~70-100 mg required.
- Do not skip HBV screening + prophylaxis — reactivation on HMA + venetoclax described.
- Do not expect a rapid response — azacitidine requires 4-6 cycles; do not stop earlier without progression.
- Do not skip G-CSF in febrile neutropenia — cumulative cytopenias expected; antimicrobial prophylaxis is mandatory.
Aggressive plan (IND-AML-1L-7-3-GO-CBF)
- Do not add GO in adverse-risk AML (TP53-mutant, complex karyotype, monosomy 7) — no benefit + toxicity persists.
- Do not use daunorubicin 90 mg/m² with GO — cardiotoxicity + early mortality signal in SWOG-S0106 was specifically due to this combination.
- Do not add GO without CD33 validation — CD33-flow ≥20% blasts required; CD33-low/negative AML — no benefit signal.
- Do not give GO within 90 days before planned alloHCT — VOD/SOS risk in the post-transplant window is dramatically increased.
- Do not skip baseline LFT + daily monitoring of bilirubin / weight gain during GO — VOD/SOS is the dominant safety concern.
- Do not skip ECHO — anthracycline cardiotoxicity + GO-specific cardiac signal require LVEF tracking.
- Do not skip TLS prophylaxis + HBV/HCV/HIV screening — standard 7+3 vigilance.
Aggressive plan (IND-AML-1L-CPX351-SECONDARY)
- Do NOT use CPX-351 in patients with de novo AML without MRC-features — FDA approval is narrow: only tAML / AML-MRC / antecedent MDS-CMML.
- Do NOT mix or substitute with free cytarabine + daunorubicin — fatal dosing errors documented (units/m² vs mg/m²).
- Do NOT prescribe with LVEF <50% — liposomal anthracycline is still cardiotoxic.
- Do NOT skip pre-cycle ECHO + cumulative-anthracycline tracking.
- Do NOT start without alloHCT-pathway planning — survival benefit predominantly via bridge to HCT.
- Do NOT stop on delayed recovery (>day 35) — this is expected for the liposomal formulation; G-CSF + transfusion support.
- Do NOT skip TLS prophylaxis in high WBC or high tumor activity.
Timeline
Treatment timeline — derived from regimen + monitoring schedule
Aggressive plan
Induction · 7+3 Induction (cytarabine + da
28-day cycles × 1 induction (re-induction if not in CR after day 14 BM); then 3-4 consolidation HiDAC cycles for younger fit; alloHCT for adverse-risk or post-CR1 in adverse / intermediate
Standard plan
Induction · Venetoclax + Azacitidine (AML,
28-day cycles × Continue until progression / unacceptable toxicity (median ~12 cycles in VIALE-A; ~25-30% achieve durable remission)
Aggressive plan
Induction · 7+3 + fractionated gemtuzumab
28-day cycles × 1 induction; consolidation HiDAC × 3-4 cycles ± additional fractionated GO 3 mg/m² day 1 of consolidation cycles 1-2 (per ALFA-0701 protocol). No upfront alloHCT in CR1 for favorable-risk per ELN 2022.
Aggressive plan
Induction · CPX-351 (Vyxeos) for tAML / AM
35-day cycles × 1-2 induction + up to 2 consolidation; alloHCT in CR1 if eligible
MDT brief
Skills (recommended) — for consideration (1)
- Clinical pharmacist recommended
Chemoimmunotherapy regimen — drug-drug interactions, dose adjustments, premedication.
skill: clinical_pharmacistv0.1.0reviewed 2026-04-25STUBsign-offs: 0lead: TBD
Open questions (1, 0 blocking)
Data quality
- Unevaluated RedFlags: RF-AML-CD33-POS-GO-CANDIDATE, RF-AML-CORE-BINDING-FACTOR-FAVORABLE, RF-AML-EMERGENCY-TLS-LEUKOSTASIS, RF-AML-FLT3-ACTIONABLE, RF-AML-FRAILTY-AGE, RF-AML-HIGH-RISK-BIOLOGY, RF-AML-IDH1-MUT-ACTIONABLE, RF-AML-IDH2-MUT-ACTIONABLE, RF-AML-INFECTION-SCREENING, RF-AML-KMT2A-ACTIONABLE, RF-AML-MEASURABLE-RESIDUAL-DISEASE, RF-AML-NPM1-MUT-FAVORABLE, RF-AML-ORGAN-DYSFUNCTION, RF-AML-SECONDARY-AML-MRC-CPX351-ELIGIBLE, RF-AML-TP53-ADVERSE, RF-AML-TRANSFORMATION-PROGRESSION
Skill catalog (1/16 activated in this plan)
All registered virtual specialists. ✓ — activated for this case; ○ — not activated (available for other clinical scenarios).
| Specialist | skill_id | Version | Last reviewed | Sign-offs | Domain |
|---|
| Cellular therapy specialist (CAR-T) | cellular_therapy_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
| Clinical pharmacist | clinical_pharmacist | v0.1.0 | 2026-04-25 | 0 | clinical_pharmacy |
| Hematologist / oncohematologist | hematologist | v0.1.0 | 2026-04-25 | 0 | hematology_oncology |
| Hematopathologist (lymphoma / leukemia / myeloma) | hematopathologist | v0.1.0 | 2026-04-25 | 0 | hematopathology |
| Infectious disease / hepatology | infectious_disease_hepatology | v0.1.0 | 2026-04-25 | 0 | infectious_diseases |
| Medical oncologist (solid-tumor chemotherapist) | medical_oncologist | v0.1.0 | 2026-04-25 | 0 | solid_oncology |
| Molecular geneticist / molecular oncologist | molecular_geneticist | v0.1.0 | 2026-04-25 | 0 | molecular_oncology |
| Palliative care | palliative_care | v0.1.0 | 2026-04-25 | 0 | palliative_care |
| Pathologist (general) | pathologist | v0.1.0 | 2026-04-25 | 0 | pathology |
| Primary care / family physician | primary_care | v0.1.0 | 2026-04-25 | 0 | primary_care |
| Psycho-oncologist | psychologist | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Radiation oncologist | radiation_oncologist | v0.1.0 | 2026-04-25 | 0 | radiation_oncology |
| Radiologist | radiologist | v0.1.0 | 2026-04-25 | 0 | diagnostic_imaging |
| Social worker / case manager | social_worker_case_manager | v0.1.0 | 2026-04-25 | 0 | psychosocial |
| Surgical oncologist | surgical_oncologist | v0.1.0 | 2026-04-25 | 0 | surgical_oncology |
| Transplant specialist (BMT) | transplant_specialist | v0.1.0 | 2026-04-25 | 0 | cellular_therapy |
Sources cited
- SRC-ALFA-0701-CASTAIGNE-2012: Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study (2012)
- SRC-ELN-AML-2022: Diagnosis and management of AML in adults: 2022 ELN recommendations from an international expert panel (2022)
- SRC-LANCET-CPX351-2018: CPX-351 (cytarabine and daunorubicin) Liposome for Injection vs Conventional Cytarabine Plus Daunorubicin in Older Patients With Newly Diagnosed Secondary AML (2018)
- SRC-NCCN-AML-2025: NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia (v.X.2025)
- SRC-RATIFY-STONE-2017: Midostaurin plus Chemotherapy for Acute Myeloid Leukemia with a FLT3 Mutation (2017)
- SRC-VIALE-A-DINARDO-2020: Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia (2020)
Experimental options (clinical trials)
Last synced: 2026-05-04 · ctgov.
No active trials matched this scenario in ctgov.
Option availability in Ukraine
Per-track UA registration · NSZU · cost · access pathway. Render-time metadata; engine selection does not depend on these fields (CHARTER §8.3).
| Option | UA registration | NSZU | Cost orientation | Access pathway |
|---|
| Aggressive plan 7+3 Induction (cytarabine + daunorubicin/idarubicin) ± midostaurin (REG-AML-7-3) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Standard plan Venetoclax + Azacitidine (AML, unfit) — VIALE-A schedule (REG-VEN-AZA-AML) | ✓ registered | ✓ covered | ₴-? — verify pathway | NSZU formulary |
| Aggressive plan 7+3 + fractionated gemtuzumab ozogamicin (CD33+ AML, 1L; ALFA-0701) (REG-AML-7-3-GO) 1/3 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
| Aggressive plan CPX-351 (Vyxeos) for tAML / AML-MRC 1L (REG-CPX351-AML) 2/2 component drug(s) not registered in Ukraine +1 | ✗ not registered | ✗ out-of-pocket | ₴-? — verify pathway | not recorded |
Cost information is orientation. Verify with a specific pharmacy / foundation / trial site. Status updated: 2026-05-04.